Principal Investigator (Young, Jessica, Carolyn): ABSTRACT The United States prescription opioid crisis is an ongoing public health concern. Since 2008, drug overdose deaths have been the leading cause of injury-related fatalities, outnumbering deaths due to motor vehicle accidents. The U.S. Food and Drug Commissioner recently stated the need to take immediate steps to address the rising toll of opioid addiction, stressing the importance of limiting lengths of opioid prescriptions to clinically relevant periods, and avoiding unnecessary opioid exposure leading to increased risk of addiction. Opioid analgesics play an important role in managing acute pain, such as that following outpatient surgery. However, patients often experience difficulty with opioid tapering and discontinuation, making prolonged opioid use the most common post-surgical complication. Long-term opioid therapy has been linked to dose escalation, increased sensitivity to pain, and increased risk of opioid addiction, abuse, and overdose. Many of those who go on to abuse opioid analgesics were first provided them in post-operative settings, and our preliminary data suggest that 75% of post-operative patients receive more dosage units than recommended by current clinical guidelines. Patient subgroups, such as those with mental health comorbidities, have reported higher levels of pain following surgery, and may be at increased risk of adverse consequences of opioid therapy. Understanding differences in prescribing to these patients and impacts of initial opioid prescriptions in this population is crucial as existing studies have suggested that these groups may be particularly vulnerable. Concurrent medications (e.g. gabapentinoids) and non-pharmacologic treatment (e.g. physical therapy, psychotherapy) may also modify the safety and effectiveness of opioids. The current project proposes to 1) describe differences in initial opioid prescription characteristics (length in days, quantity of pills, and total dosage dispensed) and concurrent use of multimodal analgesic therapies across patient subgroups, 2) estimate the effect of initial post-operative opioid prescribing on risk of long-term opioid use, opioid poisoning, and opioid addiction across a broad range of outpatient surgeries, and 3) identify vulnerable populations at higher risk of developing long-term use. This research will directly address two key clinical questions. First, our research will inform the treatment of post-surgical pain in opioid nave patients to reduce the progression of iatrogenic opioid-related problems. Second, we will provide evidence to identify concurrent medications and non-pharmacologic treatment that may modify the risks associated with opioid use in the post-operative setting. This work is timely and will identify patterns in opioid prescribing that can be translated into meaningful interventions targeted at reduced long-term opioid use and the serious sequelae thereof.